Alpha-4 integrins and VCAM-1, but not MAdCAM-1, are essential for recruitment of mast cell progenitors to the inflamed lung
Alpha-4 integrins and VCAM-1, but not MAdCAM-1, are essential for recruitment of mast cell progenitors to the inflamed lung
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DOI：
10.1182/blood-2005-12-012781
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发表时间：
2006-09-01
期刊：
影响因子：
20.3
通讯作者：
Gurish, Michael F.
中科院分区：
文献类型：
--
作者：
Abonia, J. Pablo;Hallgren, Jenny;Gurish, Michael F.
正常小鼠的肺缺乏数量可观的肥大细胞（MC）或MC祖细胞（MCp），但在气管支气管上皮表面的成熟MC的外观是过敏性，T细胞依赖性肺部炎症的特征。我们假设肺部炎症会将MCp募集到发炎的肺部，并且这种募集会受到不同粘附途径的调节。卵清蛋白致敏和激发小鼠肺中MCp数量增加超过28倍。在缺乏内皮血管细胞粘附分子1（VCAM-1）的小鼠和给予VCAM-1阻断性单克隆抗体（mAb）但不给予粘膜地址素CAM-1（MadCAM-1）的野生型小鼠中，MCp向发炎肺的募集减少了75%以上。VCAM-1的整联蛋白受体分析显示，在β 7整联蛋白缺陷小鼠中，募集相对于野生型对照减少73%，并且在BALB/c或C57 B/L 6小鼠中，α 4、β 1或β 7整联蛋白的mAb阻断抑制MCp向发炎肺的募集。因此，VCAM-1与α 4 β 1和α 4 β 7整联蛋白的相互作用对于抗原诱导的肺部炎症期间肺中MCp群体的募集和扩增是必不可少的。此外，MCp目前在炎性细胞中是独特的，其部分依赖于α 4 β 7整联蛋白用于肺募集。
Normal mouse lungs lack appreciable numbers of mast cells (MCs) or MC progenitors (MCp's), yet the appearance of mature MCs in the tracheobronchial epithelial surface is a characteristic of allergic, T-cell-dependent pulmonary inflammation. We hypothesized that pulmonary inflammation would recruit MCp's to inflamed lungs and that this recruitment would be regulated by distinct adhesion pathways. Oval bumin-sensitized and challenged mice had a greater than 28-fold increase in the number of MCp's in the lungs. In mice lacking endothelial vascular cell adhesion molecule 1 (VCAM-1) and in wild-type mice administered blocking monoclonal antibody (mAb) to VCAM-1 but not to mucosal addressin CAM-1 (MadCAM-1), recruitment of MCp's to the inflamed lung was reduced by greater than 75%. Analysis of the integrin receptors for VCAM-1 showed that in beta 7 integrin-deficient mice, recruitment was reduced 73% relative to wild-type controls, and in either BALB/c or C57B/L6 mice, mAb blocking of alpha 4, beta 1, or beta 7 integrins inhibited the recruitment of MCp's to the inflamed lung. Thus, VCAM-1 interactions with both a4 beta 1 and alpha 4 beta 7 integrins are essential for the recruitment and expansion of the MCp populations in the lung during antigen-induced pulmonary inflammation. Furthermore, the MCp is currently unique among inflammatory cells in its partial dependence on a4 beta 7 integrins for lung recruitment.